Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India; Centre for Pharmacology and Therapeutics, Rosewell Park Comprehensive Care Centre, 665 Elm Street, Buffalo, NY, USA 14203.
Life Sci. 2023 May 15;321:121535. doi: 10.1016/j.lfs.2023.121535. Epub 2023 Mar 9.
MicroRNAs are critical regulators of the plethora of genes, including FOXO "forkhead" dependent transcription factors, which are bonafide tumour suppressors. The FOXO family members modulate a hub of cellular processes like apoptosis, cell cycle arrest, differentiation, ROS detoxification, and longevity. Aberrant expression of FOXOs in human cancers has been observed due to their down-regulation by diverse microRNAs, which are predominantly involved in tumour initiation, chemo-resistance and tumour progression. Chemo-resistance is a major obstacle in cancer treatment. Over 90% of casualties in cancer patients are reportedly associated with chemo-resistance. Here, we have primarily discussed the structure, functions of FOXO and also their post-translational modifications which influence the activities of these FOXO family members. Further, we have addressed the role of microRNAs in carcinogenesis by regulating the FOXOs at post-transcriptional level. Therefore, microRNAs-FOXO axis can be exploited as a novel cancer therapy. The administration of microRNA-based cancer therapy is likely to be beneficial to curb chemo-resistance in cancers.
微小 RNA 是大量基因的关键调节因子,包括 FOXO“叉头”依赖转录因子,它们是真正的肿瘤抑制因子。FOXO 家族成员调节细胞凋亡、细胞周期停滞、分化、ROS 解毒和寿命等核心细胞过程。由于多种 microRNAs 的下调,FOXO 在人类癌症中的表达异常,这些 microRNAs 主要参与肿瘤起始、化疗耐药和肿瘤进展。化疗耐药是癌症治疗的主要障碍。据报道,超过 90%的癌症患者的死亡与化疗耐药有关。在这里,我们主要讨论了 FOXO 的结构和功能,以及影响这些 FOXO 家族成员活性的翻译后修饰。此外,我们还讨论了 microRNAs 通过在转录后水平调节 FOXO 在致癌作用中的作用。因此,microRNA-FOXO 轴可以被开发为一种新的癌症治疗方法。microRNA 为基础的癌症治疗的管理可能有利于遏制癌症中的化疗耐药性。